短双歧杆菌CCFM683对肠道屏障的保护机制

肠道屏障由机械屏障、免疫屏障和生物屏障等组成，对人体健康起重要作用，而益生菌的益生功能与其保护肠道屏障的作用密不可分，但目前关于益生菌调节肠道屏障的分子机制、信号通路和关键物质基础的研究仍十分有限。申请人前期研究发现短双歧杆菌CCFM683可调节粘蛋白、肠道固有层细胞因子、肠道微生物等。本项目拟聚焦于该菌，从上皮细胞、紧密连接、固有层和肠系膜淋巴结免疫细胞以及相互间信号通路入手，深入研究该菌保护肠道屏障的分子机制；结合代谢组、基因组和分子生物学手段，明确该菌改善肠道屏障的关键物质基础；并解析该菌在肠道轴向分布以及产生和积累关键物质的生态位，为解析益生菌发挥益生功能的物质基础、分子机制及应用提供理论依据和新方向。

Intestinal barrier is composed of mechanical barrier, immune barrier and biological barrier, which plays an important role in human health. The benefits of probiotics are closely related to its intestinal barrier protection. However, the current research on molecular mechanism, signal pathway and crucial metabolites of probiotics regulating intestinal barrier is limited. In our previous study, Bifidobacterium breve CCFM683 could regulate mucin, intestinal lamina propria cytokines and gut microbiota. This current project aims to further explore the protection mechanism of the strain on intestinal barrier, with the analyses on epithelial cells, tight junction, lamina propria and immune cells of mesenteric lymph nodes as well as the signal pathway among them. Then combined with metabolomics, genomics and molecular biological approaches, the key metabolite in the strain for improving intestinal barrier will be confirmed; in addition, the distribution of the strain in the gastrointestinal tract and the ecological niches for generating and accumulating the key metabolite will be investigated. The findings in the project will provide new theoretical basis and new guidance to analyze the curial substances, mine molecular mechanism and develop novel application of probiotics.